Insulin increases H2O2-induced pancreatic beta cell death.

Insulin resistance results, in part, from impaired insulin signaling in insulin target tissues. Consequently, increased levels of insulin are necessary to control plasma glucose levels. The effects of elevated insulin levels on pancreatic beta (ß) cell function, however, are unclear. In this study, we investigated the possibility that insulin may influence survival of pancreatic ß cells. Studies were conducted on RINm, RINm5F and Min-6 pancreatic ß-cells. Cell death was induced by treatment with H(2)O(2), and was estimated by measurements of LDH levels, viability assay (Cell-Titer Blue), propidium iodide staining and FACS analysis, and mitochondrial membrane potential (JC-1). In addition, levels of cleaved caspase-3 and caspase activity were determined. Treatment with H(2)O(2) increased cell death; this effect was increased by simultaneous treatment of cells with insulin. Insulin treatment alone caused a slight increase in cell death. Inhibition of caspase-3 reduced the effect of insulin to increase H(2)O(2)-induced cell death. Insulin increased ROS production by pancreatic ß cells and increased the effect of H(2)O(2). These effects were increased by inhibition of IR signaling, indicative of an effect independent of the IR cascade. We conclude that elevated levels of insulin may act to exacerbate cell death induced by H(2)O(2) and, perhaps, other inducers of apoptosis.

Quantitative assessment of valvular regurgitations using the pulsed Doppler technique. Approach to the regurgitant lesion.

It is now possible with pulsed Doppler to grade the severity of aortic, mitral and tricuspid regurgitations on a quantitative basis. "Indices" were devised, using the measurement of the spatial extent of abnormal Doppler signals. For aortic regurgitation: (1) at the aortic valvular orifice area, by measurement of the regurgitant aortic valvular area and calculation of the valvular regurgitant "index". (2) In the left ventricle outflow tract, by calculation of an "index" combining information from two echographic (short and long axis) planes. For mitral regurgitation: by calculation of the total regurgitant "index" combining information from examination of the annulus in short axis, and of the left atrium in long axis view. For tricuspid regurgitation: at the tricuspid annulus, by averaging the depth of the reversal wave on two samples recorded using various echographic approaches. A group of patients with aortic (42), mitral (55) and tricuspid (57) regurgitation proven by invasive procedures, was investigated with this procedure using a 3 MHz two dimensional pulsed Doppler echo device. Correlative coefficients between the Doppler grading and that provided by independently performed invasive procedures on a three point scale, ranged between 0.66 and 0.88, with significant differentiation of mean values of indices (P less than 0.01 to P less than 0.001) for each grade of severity. Success in the Doppler grading of severity of the regurgitations requires (1) a sampling as close as possible to the lesion, and optimally at ther very site of the lesion, (2) the largest explorable area at the site of the lesion, (3) the relevancy of the selected Doppler parameter in order to take into account, as much as possible, the three dimensional configuration of the regurgitant jet. Moreover, this mapping procedure provides a pathophysiological insight of the regurgitant lesion for left-sided regurgitations.

Variability in the period of the blood pressure circadian rhythm in human beings.

In studies and assessments of human beings done in natural settings, it is assumed that the period tau of circadian rhythms, including ones of systolic (SBP) and diastolic (DBP) blood pressure, is equal to 24 hours. To test this hypothesis, SBP and DBP rhythms were studied in 112 medication-free, non-hospitalized subjects (62 males, 47.1 + 2.0 years [x +/- SEM], and 50 females, 54.5 +/- 2.1 years) by 48 h ambulatory blood pressure monitoring (ABPM). Of these, 26 were hypertensive (diurnal SBP > 140 mmHg and diurnal DBP > 90 mmHg) and 86 normotensive. All subjects were synchronized by their habitual daytime activities from approximately 08:00 h to approximately 23:00 h +/- 1 h and by sleep at night. The BP was assessed at 15-minute intervals during a continuous 48h span using a Spacelabs model #90207 ABPM. The time series data of each subject were individually evaluated by power spectra analysis for the prominent tau of the SBP and DBP rhythms. The prominent tau differed from 24 hours in 22/112 subjects for SBP and in 16/112 subjects for DBP. Generally, in these individuals the tau was less than 24 hours. The occurrence of non-24 h tau's was more frequent in hypertensive than normotensive subjects; the difference between the groups in the distribution of the prominent tau's by class (tau = 24 h, tau = 12, 12 h > tau < 24 h, etc.) was statistically significant (chi 2 test = 19.1; p < 0.001). No difference in the distribution of tau's of blood pressure was detected according to the subject's age and gender. These findings suggest that ABPM done only for a duration of 24 h may be too short to characterize accurately the features of the day-night variation in human BP, including the precise period of its rhythm.

Comparison of two levels of vitamin C supplementation on antioxidant vitamin status in elderly institutionalized subjects.

The concentrations of antioxidant vitamins, particularly vitamin C, are often low in the plasma of institutionalized elderly subjects, and could explain their susceptibility to oxidative stress. However, as such low levels were not always found in home-living healthy elderly persons, the antioxidant vitamin depletion in the formers could result from environmental conditions better than aging itself. The objective of this study was therefore to verify the antioxidant vitamin status in institutionalized elderly persons and to evaluate if a low vit C supplement could be sufficient to improve the plasma vit C concentration in those subjects. This study confirms that plasma vitamin C levels are in the scurvy range in 20 elderly institutionalized subjects and significantly lower than in healthy home-living elderly persons. Beta-carotene concentrations were found marginally low but alpha-tocopherol levels were in the normal range. All three vitamins were correlated. Fifteen days on a physiological vitamin C (150 mg/day) supplementation was sufficient to restore normal vit C levels (50 mumol/l). A further pharmacological vit C administration (750 mg/day) during 30 days only allowed a marginal increase in the plasma vit C concentrations.

[Pulsed echo-Doppler diagnosis and evaluation of tricuspid valve, and interventricular and interatrial communication insufficiencies. Flowmeter study of shunts]. / Diagnostic et évaluation par écho-Doppler pulsé des insuffisances tricuspidiennes et des communications interventriculaires et interauriculaires. Etude vélocimétrique des shunts.

A group of 44 patients with a total of 48 cardiac lesions ( 22 tricuspid incompetence - TI - , 12 ventricular septal defect - VSD - and 14 atrial septal defect - ASD - , and two control groups of 20 normals and 23 patients with other cardiac disease , were studied by pulsed Doppler echocardiography ( PDE ) . The flow patterns recorded in the normal right heart were identical to those recorded previously during catheterisation . TI was diagnosed by the presence of an abnormal negative systolic wave usually associated with widening of the time interval histogram with a specificity of 82 % and a sensitivity of 86 % . An acceptable semi-quantative assessment of the severity of regurgitation was obtained in 83 % by comparing the amplitude of the negative systolic wave with that of the positive diastolic wave . Shunts were diagnosed by detecting septal or tricuspid turbulence with a sensitivity of 83 % and a specificity of 90 % . A satisfactory assessment of the size of the shunt was obtained in 90 % of diagnosed cases by assessing the pulmonary and infundibular flow patterns . A systolic wave starting with isometric contractions , followed by positive early and late diastolic waves and some intermediary negative oscillations of variable amplitude were recorded along the right side of the interventricular septum in 75 % of VSDs . In 78 % cases of ASD a large late systolic - early diastolic wave overriding the second heart sound , followed by positive mid and late diastolic waves of variable size , according to the heart rate , were recorded in the right atrium . In conclusion , PDE recording of blood flow patterns and turbulence in the right heart is a useful non-invasive method of diagnosis and assessment of these three cardiac lesions . It provides a valuable contribution towards the physiopathological study of shunt patterns in atrial and ventricular septal defects .

[Doppler technics in the study of prosthetic valves]. / Contribution des techniques Doppler à l'étude des prothèses valvulaires.

The authors studied a group of 120 patients and a total of 137 valvular prostheses by ultrasonic pulsed Doppler (3 MHz). Fifty three of these prostheses were also investigated with continuous wave Doppler. Clinical, phonocardiographic and echocardiographic examination revealed 99 normal and 38 abnormal prostheses, the latter group comprising 42 dysfunctions (9 obstructions and 33 regurgitations), all confirmed by invasive studies. The lesions were graded into 3 degrees of severity. The methods used were the recording of velocity signals and two- and three-dimensional mapping in the pulsed Doppler mode, and the calculation of the haemodynamic parameters derived from measurements of blood velocity in the continuous wave mode. Pulsed Doppler correctly diagnosed 92 out of the 99 normal prostheses. The maximum systolic pressure gradient in aortic valve prostheses was 16 +/- 6 mmHg; the average early diastolic pressure gradient of the mitral valve prostheses was 10.01 +/- 3.34 mmHg, with a mean diastolic gradient of 4.52 +/- 0.71 mmHg and a mean pressure half time of 0.09 +/- 0.02 sec giving an average valve surface area of 2.45 +/- 0.57 cm2. The sensitivity and specificity of the diagnosis of valve dysfunction were 95 and 92 per cent respectively with a satisfactory evaluation of the degree of severity in 88 per cent of cases. In the 3 mitral valve prostheses with obstruction, significant abnormalities of pressure half time and value surface area were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

[Characteristics of jets in adult bicuspid aortic valve by color Doppler imaging]. / Caractéristiques des jets sur bicuspidie aortique de l'adulte en imagerie Doppler couleur.

Color flow mapping of 15 adults with bicuspid aortic valves confirmed angiographically and at surgery comprising 8 regurgitations and 7 stenoses was analysed, retrospectively in 12 cases. The object was to detect any special features of the jets of this congenital abnormality. The site of emergence of the jet at the aortic orifice and its direction in the left ventricle were studied in the long axis, short transaortic and left ventricular axes by sequential analysis. Two types of regurgitant jet were observed: eccentric anterior origin (5, Type I), eccentric posterior origin (3, Type II), extending towards the structure opposite to their origin in the left ventricular outflow tract. In cases of stenosis, the cross-sectional view of the jet had an almost transverse slit-like appearance extending from one side of the aortic orifice to the other or an anterior or posterior eccentric oval shape. The Type I cases and the slit-like anterior stenoses had fusion of the coronary cusps whilst the Type II and posterior slit-like stenoses had fusion of the right coronary and non-coronary cusps. This preliminary study suggests that bicuspid aortic valves are associated with jet characteristics related to the abnormal commissural axis which allows diagnosis and precision of the anatomic type in adults despite the presence of calcification.

[Chronology of maximal surface area and peak velocities of left heart valve flow jets using Doppler imaging. Clinical implications]. / Chronologies des aires maximales en imagerie doppler et du pic de vélocité en doppler continu des jets valvulaires gauches. Implications cliniques.

The aim of this study was to correlate the timing of the maximal surface area of the jet recorded by color flow Doppler and the peak velocities recorded by continuous mode Doppler with reference to the ECG R wave to determine whether standardisation of the chronologies of measurements was possible. A comparative paired study of these two parameters was undertaken in 44 subjects who had 55 left heart valvular lesions, all in sinus rhythm and, in cases of regurgitation, with pansystolic or pandiastolic regurgitant flow. The jets were examined in the inflow chambers of valvular insufficiency and at the origin of the jet in the short axis for stenotic lesions and aortic regurgitation, with planimetry of the cross sectional area in color Doppler. The correlation coefficient was 0.85 for aortic stenosis, 0.96 for mitral stenosis, 0.84 for aortic regurgitation but only 0.10 for mitral regurgitation. The mean values of the two chronologies were identical for stenotic lesions and did not differ significantly in regurgitation even at the mitral valve. However, the individual differences between the two chronologies exceeded 20 ms in 63% of aortic and 91% of mitral regurgitations. The maximal surface areas of the jets of 45% of aortic regurgitant and 91% of mitral regurgitant lesions were recorded between the onset of regurgitation and the peak jet velocity. The differences in chronology of the two parameters studied in cases of valvular regurgitation indicate the multifactorial nature of color flow jet imaging, probably associated with individual physiopathological variations.(ABSTRACT TRUNCATED AT 250 WORDS)

[A new quantitative method for quantifying left heart jets by Doppler color imaging]. / Nouvelle approche méthodologique quantitative des jets valvulaires gauches en imagerie Doppler couleur.

Quantification of valvular lesions by Color Doppler is based on jet measurements. The aim of this new method is to reduce some of the errors in these measurements: uncertainty in delimiting the colored areas of the jets; spontaneous beat-to-beat variations of the jets entailing interpretative difficulties. The first step was to determine the correlations between the colored areas and previously established single-gated Doppler criteria, retaining spectral criteria to define the borders of the jets, so overcoming some of the limitations of color Doppler. The association of these methods resulted in better discrimination between grades and a better correlation in 45 angiographically controlled mitral and aortic regurgitations than with color Doppler alone. In stenotic lesions, spectral criteria from single-gated associated exploration enabled localisation of the level for planimetry of the section of the jet at its origin visualised by color Doppler. Satisfactory correlations were obtained with the Gorlin surface area in a group of 43 patients with mitral and aortic stenosis. A coefficient of variation of 13 to 14 per cent was found with planimetry of the regurgitant jet in the upstream cardiac chamber. Uni-dimensional measurement decreased this variation to 6 to 11 per cent in the same patients. The largest decrease in variability (6 to 8 per cent) was observed in stenotic and regurgitant lesions with planimetry of the section of jet at its origin performed in held mid-expiration and so this would appear to be the best method. The guide lines and technological improvement associated with the physiopathological information provided by color Doppler should refine the quantification of valvular heart lesions.

[Clinical value of the detection of diastolic mitral regurgitation by pulsed Doppler]. / Intérêt clinique de la détection par Doppler pulsé des régurgitations mitrales diastoliques.

The reliability of pulsed Doppler echocardiography for the detection of mitral diastolic regurgitation was evaluated in 21 patients with severe aortic insufficiency and/or cardiomyopathy. Among these patients, 17 had sinus rhythm with a normal PR interval, while 4 had atrial fibrillation with short or normally lasting diastoles. Detection was negative in 10 cases (group A) and positive in the remaining 11 cases (group B). In all patients the data supplied by Doppler echocardiography were confirmed by angiography (100% sensitivity and specificity). A comparative study of right heart and left heart pressures in the two groups showed that group B patients had a special pressure profile, the most significant feature of which was an increase in pulmonary arterial and capillary pressures (p less than 0.01 and p less than 0.001 respectively). The diagnostic reliability of mitral valve diastolic regurgitation as to the presence of an abnormal mean pulmonary pressure was: sensitivity 80%, specificity 73%. Right heart pressures were either normal or very slightly elevated in group A patients. It is concluded that the presence of mitral diastolic regurgitation in patients with the pathology described indicates an unfavourable prognosis. This should be taken into account and lead to a systematic of mitral flow in these patients.

[Analysis of prognostic factors in cervicofacial carcinology using the Cox model. An example of piriform sinus cancer]. / L'analyse des facteurs pronostiques en carcinologie cervico-faciale par le modèle de Cox. Un exemple à propos du cancer du sinus piriforme.

Analysis of prognosis factors was performed on a surgical series of 34 of piriform sinus cancer, based on the use of a multivariate study according to the Cox model. The presentation is essentially didactic emphasizing the main points: how to collect data, what data to collect, and what judgment criterion to use. The authors detail the interpretation to be drawn from the analysis results using Cox model.

Non-invasive diagnosis and assessment of aortic valve disease and evaluation of aortic prosthesis function using echo pulsed Doppler velocimetry.

Non-invasive recording of aortic blood flow velocity patterns in the ascending aorta and in the arch of the aorta was performed in 12 normal subjects, 38 patients with confirmed aortic valve disease, and 13 patients with aortic prostheses using pulse echo Doppler velocity recordings. In normal subjects, the velocity recordings correlated well with those obtained by other authors using invasive procedures. In patients with aortic valve disease, specific abnormalities of the velocity curves were found to correlate well both with the type of lesion (stenosis or regurgitation) and its severity on a three-point scale. Both sensitivity and specificity were found to range between 80 and 94 per cent. A less accurate grading of severity was obtained from patients with aortic regurgitation by the detection of turbulence in the left ventricular outflow tract than from the appearance of the aortic velocity curves. In the studies of patients with aortic prostheses, anomalies of the velocity pattern could be found in the ascending aorta in 53 per cent but no abnormalities of timing was found. In spite of some technical limitations, pulse echo Doppler velocity recordings provide a new non-invasive, reliable, and reproducible approach in assessing the presence and severity of aortic lesions and demonstrating flow abnormalities produced by prostheses.

Applications of pulsed Doppler flow mapping to left sided cardiac valvular lesions.

The flow mapping procedure has been developed in parallel to the standard pulsed Doppler procedure. It has a different purpose--picking up flow signals at the site of lesions rather than calibrating velocities--and has its own methodology, developed within the last six years. On the basis of invasive correlations performed in 267 cases of valvular heart disease, we review the three-fold purpose of the flow mapping technique: diagnosing lesions, relying on the presence of flow anomalies; assessing their severity, relying on the spatial spreading of these flow signals; and identifying the site of the lesion, which is a specific advantage, relying on the anatomical location of these flow signals and/or on the direction of the jets. For example, using this technique, it is now possible to easily differentiate a cusp tear from a leak of a bioprosthesis, to measure the size of the leaks, and to reconstruct the image of aortic or mitral stenotic areas. These optimal results are only obtained using an appropriate methodology which mainly includes a) the selection of adequate two-dimensional short axis planes in order to explore the diseased valve in its entirety, because of frequent assymetrical orifices, and to pick up the jets at their starting point, b) measurements of the abnormal areas, c) when jets are studied, a three dimensional approach is required in order to cope with the three dimensional nature of the jet and to make available the calculation of three dimensional indices of severity.(ABSTRACT TRUNCATED AT 250 WORDS)

New indexes for assessing aortic regurgitation with two-dimensional Doppler echocardiographic measurement of the regurgitant aortic valvular area.

Direct examination of the aortic orifice at the level of the aortic valves (aortic valvular orifice area, AVOA) in the short-axis plane was performed with a 3 MHz two-dimensional pulsed Doppler echocardiographic apparatus. The AVOA was mapped with the Doppler gate to detect or rule out the presence of a regurgitant aortic valvular area (RAVA) established by recording of abnormal diastolic Doppler signals on a "yes or no" basis. A group of 12 normal subjects and 83 patients, including 40 patients with aortic regurgitation proven by aortography, were investigated with this procedure. In the 38 patients with aortic regurgitation diagnosed by Doppler echocardiography (diagnostic sensitivity 95%, specificity 100%), planimetric measurements of the RAVA and AVOA were performed with calculation of two indexes: the RAVA/square meter of body surface area and the RAVA/AVOA ratio. These indexes correlated well with independently performed angiographic grading on a three-point scale (r = .87 for the RAVA, .88 for the RAVA/AVOA; p less than .001), with highest significance of differences in mean values among each grade of severity found for the RAVA/AVOA (p less than .001). In addition, Doppler echocardiography identified the anatomic valvular site of the lesion, and we confirmed the site during surgery.

Calculation of pulsed Doppler left ventricular outflow tract regurgitant index for grading the severity of aortic regurgitation.

Measurement of the spatial extent of the regurgitant jet was performed in the left ventricular outflow tract (LVOT) with a 3 MHz two-dimensional echo-pulsed Doppler device, in order to assess the severity of aortic regurgitation on a quantitative basis. The procedure included: detection of diastolic disturbances in the LVOT and mapping of these disturbances in the LVOT. Length (L) and height (H) were measured with calculation of the product (L X H) in the long-axis view and width (W) in the short-axis view with calculation of the LVOT regurgitant index (LVOTRI) as follows: ([L X H] X W). Twelve normal subjects and a group of 83 patients, including 40 patients with aortic regurgitation proved by aortography, were investigated with this procedure. Diagnostic reliability ranged between 90% for specificity and 95% for sensitivity. Correlations between the grading provided by the LVOTRI and those provided by aortography on a three-grade scale showed a correlation coefficient between 0.67 (linear model, p less than 0.01) and 0.80 (exponential model), because of the high values of the index in cases of severe regurgitation. Reliability of the LVOT investigation in aortic regurgitation requires the use of information from two combined scan planes and quantitative rather than qualitative data. Main limitations of the procedure are due to the presence of associated mitral lesions.

Detection of diastolic mitral regurgitation using pulsed Doppler and its implications.

Diastolic mitral regurgitation has been angiographically demonstrated in some patients with severe aortic regurgitation and/or nonobstructive cardiomyopathy. The purpose of this paper was two-fold: to study the feasibility of pulsed Doppler noninvasive detection of this unusually timed regurgitation on the basis of angiographic correlations in a group of 21 patients with such conditions and sinus rhythm with normal PR interval in 81% of the cases, and when diastolic mitral regurgitation was present, to study if it had clinical implications. Doppler detection was feasible in all cases and there were no false positive diagnoses. Comparison of haemodynamic data in patients without (group A) and with (group B) diastolic mitral regurgitation showed a significant increase in the mean values of pressures, particularly for the mean pulmonary artery and capillary wedge pressures (P less than 0.01 to 0.001), in group B. This study suggests that the recording of mitral flow velocity should be routinely performed in patients with such pathological conditions, since the finding of diastolic mitral regurgitation may have clinical significance.